title: The IgH 3' regulatory region controls somatic hypermutation in germinal center B cells.
abstract: Interactions with cognate antigens recruit activated B cells into germinal centers where they undergo somatic hypermutation (SHM) in V(D)J exons for the generation of high-affinity antibodies. The contribution of IgH transcriptional enhancers in SHM is unclear. The Eμ enhancer upstream of Cμ has a marginal role, whereas the influence of the IgH 3' regulatory region (3'RR) enhancers (hs3a, hs1,2, hs3b, and hs4) is controversial. To clarify the latter issue, we analyzed mice lacking the whole 30-kb extent of the IgH 3'RR. We show that SHM in VH rearranged regions is almost totally abrogated in 3'RR-deficient mice, whereas the simultaneous Ig heavy chain transcription rate is only partially reduced. In contrast, SHM in κ light chain genes remains unaltered, acquitting for any global SHM defect in our model. Beyond class switch recombination, the IgH 3'RR is a central element that controls heavy chain accessibility to activation-induced deaminase modifications including SHM.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS) UMR 7276, Université de Limoges, 87025 Limoges, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Rouaud
authors.forename: Christelle
authors.initials: C
authors.lastname: Vincent-Fabert
authors.forename: Alexis
authors.initials: A
authors.lastname: Saintamand
authors.forename: Rémi
authors.initials: R
authors.lastname: Fiancette
authors.forename: Marie
authors.initials: M
authors.lastname: Marquet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Robert
authors.forename: Bernardo
authors.initials: B
authors.lastname: Reina-San-Martin
authors.forename: Eric
authors.initials: E
authors.lastname: Pinaud
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D012045:Regulatory Sequences, Nucleic Acid; D027041:Somatic Hypermutation, Immunoglobulin; D014158:Transcription, Genetic; D050441:VDJ Exons; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D020413:3' Untranslated Regions; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase